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What Causes Prurigo Nodularis?

Posted on September 21, 2022
Medically reviewed by
Kevin Berman, M.D., Ph.D.
Article written by
Emily Wagner, M.S.

Prurigo nodularis (PN), also known as nodular prurigo, is an inflammatory skin disease that causes nodules, papules, or lesions and intense itchiness (pruritus). Researchers aren’t sure of the exact cause of the condition, but they believe it may be due to issues with the immune system and nerves in the skin.

PN is associated with several risk factors, both inherited and environmental. Inherited risk factors are passed down from parents to their children in DNA. These risk factors cannot be controlled. On the other hand, environmental risk factors include exposure to certain medications, age, or other chronic health conditions.

The Skin and Prurigo Nodularis

PN makes a person’s skin extremely itchy, causing those with the condition to pick and scratch at the skin. All that scratching can cause your skin to thicken, resulting in raised bumps that continue to itch. An itch-scratch cycle can develop, which can be difficult to break — even if you use anti-itch creams and pills.

The Role of the Nervous System

Skin studies of people living with PN have yielded clues as to why some people develop the condition.

It helps to first understand the three layers that make up the skin:

  • Epidermis — The thin outermost layer that protects the body from outside elements
  • Dermis — The thick layer of living tissue below the epidermis that contains blood capillaries, nerve endings, sweat glands, and hair follicles
  • Hypodermis — The bottom layer that serves several functions, including storing fat energy, providing insulation and padding, and attaching the skin to bones and muscle

Researchers have found that people with PN have more nerve fibers in the dermis and fewer in the epidermis compared to those who don’t have PN. They believe the excess of these nerve fibers may make people feel more itchiness, which causes PN symptoms. The cause of this is not clear, but scratching may contribute to it.

The Role of the Immune System

People with PN also have different skin composition compared to those who don’t have the condition. Studies have found that there are more inflammatory immune cells present in PN, including mast cells and neutrophils. Mast cells are responsible for creating allergy symptoms because they release the chemical histamine. This typically causes itchy skin and hives, and it’s also connected to the development of eczema. Other immune cells help recruit inflammatory cells by releasing special chemical signals known as cytokines.

Altogether, the combination of increased nerve fibers and inflammation likely causes the intense itchiness associated with PN.

Inherited Risk Factors

Inherited factors are passed down through generations. Oftentimes, these are seen as mutations in genes that increase a person’s chances of developing a condition or disease. However, researchers haven’t found an exact gene linked to developing PN.

Race and ethnicity may affect a person’s chances of developing PN. A study of 909 people with PN found that African American participants were 3.4 times as likely to have the condition than white participants. However, race and ethnicity can often tie into environmental risk factors that complicate these associations.

Environmental Risk Factors

Environmental factors can increase a person’s risk of developing PN. These include:

  • Age and sex
  • Exposure to certain cancer medications
  • Underlying health conditions
  • Certain infections

Many of these factors involve the overactivation of the immune system, further contributing to the inflammation believed to drive PN.

Age and Sex

Age and sex play a large role in who develops PN. According to the American Academy of Dermatology Association, people 50 and older are more likely to develop the condition, especially those between the ages of 51 and 65. Women are also more likely to have PN than men, accounting for 54.2 percent of cases, according to NORD.

Though most cases of PN appear in older individuals, younger people can also develop the condition. However, most younger people who have PN also have other inflammatory or allergic conditions, such as atopic dermatitis (eczema).

Medication

Almost all medications come with side effects, and this is especially true for cancer treatments. Researchers believe that some people may develop PN after undergoing certain cancer treatments that overactive their immune systems to help fight off the cancer. Medications that may cause PN include the chemotherapy drugs carboplatin and paclitaxel, along with the immunotherapy drug pembrolizumab.

Related Conditions

PN may develop on its own or along with other skin conditions, infections, or diseases. Treatments for other conditions may also increase a person’s risk for developing PN.

Other Skin Disorders

People with PN have more inflammatory immune cells in their skin, and it’s common for them to have additional skin disorders. These include:

  • Cutaneous T-cell lymphoma, a type of cancer that causes the immune system to attack skin cells
  • Bullous pemphigoid, which causes fluid-filled blisters to form
  • Atopic dermatitis
  • Xerosis cutis, which is chronically dry skin
  • Keratoacanthoma, a type of skin cancer
  • Lichen planus, which causes inflammation of the mucous membranes along with itchy skin

Bacterial, Viral, and Parasitic Infections

When you contract an infection, your immune system activates to help fight off the invading pathogens. Bacterial, viral, and parasitic infections can also cause PN to flare up, likely because the immune system is in overdrive fighting the infection.

Some causes of PN include:

  • Mucogenicum, which causes skin infections
  • Helicobacter pylori, which is responsible for causing ulcers
  • Tuberculosis
  • Hepatitis C
  • HIV
  • Herpes zoster, or shingles, which results in itchy skin lesions

Systemic Diseases

Other systemic (whole-body) diseases that can cause the skin to itch are also associated with an increased risk of developing PN. In some cases, treating the underlying disease helps treat PN, but this is not always true. These include:

  • Blood cancers, such as lymphoma and multiple myeloma
  • Diabetes
  • Anemia caused by low iron levels
  • Liver disease
  • Thyroid disease and related problems, including hyperparathyroidism
  • Kidney disease
  • Celiac disease
  • Gout
  • Polycythemia vera, a type of myelodysplastic syndrome
  • Skin cancer
  • Other types of cancer, including those in the bladder, lung, liver, gastrointestinal tract, and female reproductive organs

Mental Health Conditions

Mental health is also associated with the development of PN. People living with depression or anxiety may develop what’s called psychogenic itch. This type of itch is not caused by a skin condition, but enough picking and scratching at the skin can trigger PN to develop.

Can Prurigo Nodularis Be Prevented?

Unfortunately, there is no one way to prevent the development of PN. If you have another health condition that may be contributing to PN, treating that condition can sometimes help PN symptoms, but it may not resolve.

If you begin noticing symptoms of PN, talk to your doctor about ways to manage them. Treatment for prurigo nodularis, such as topical corticosteroids, phototherapy, and antihistamines, can help prevent flares and break the itch-scratch cycle.

Find Your Team

On MyPrurigoTeam, the social network for people with prurigo nodularis and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with prurigo nodularis.

Are you living with prurigo nodularis? Share your experience in the comments below, or start a conversation by posting on your Activities page.

All updates must be accompanied by text or a picture.
Kevin Berman, M.D., Ph.D. is a dermatologist at the Atlanta Center for Dermatologic Disease, Atlanta, GA. Review provided by VeriMed Healthcare Network. Learn more about him here.
Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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